Schistosomiasis is an important tropical parasitic human disease. Although an effective anti-schistosome drug is in use, it is estimated that 200 million people are infected, 20 million individuals suffer severe disease symptoms, and 280,000 people die annually from schistosomiasis. Although the genome sequences of Schistosoma mansoni and S. japonicum have been determined, most predicted genes encode proteins with unknown function. In order to make full use of the genome sequence databases it is imperative to develop efficient and reproducible functional genomic tools. In this application we propose to develop moderate throughput imaging methodologies that will enable tissue expression localization of a gene. Because of the importance of the worm egg in transmission of the lifecycle and pathology of schistosomiasis, this proposal focuses on expression localization of genes involved in reproductive biology of the worm, which we have identified in a transcriptional analysis of worm development. By co-localizing genes of unknown function with genes with known functions we will be able to understand their functions and to develop protein interacting networks. Parasitic flatworms require a host to complete their lifecycles and have generally poorly developed functional genomic tools. Therefore, we will determine if a free living flatworm with a well-developed functional genomic toolbox, Schmidtea mediterranea, can be used to investigate fundamental processes in parasitic flatworms. Our long-term goals are to identify new drug targets and vaccine candidates for schistosomiasis control.